Thyroid hormone and glucocorticoid independently regulate the expression of estrogen receptor in male Xenopus liver cells.

Earlier studies from our laboratory had shown that triiodothyronine (T3) strongly potentiates the activation by estradiol (E2) of silent vitellogenin (Vit) genes and the autoinduction of estrogen receptor (ER) mRNA in primary cultures of male Xenopus hepatocytes (Rabelo and Tata, 1993). It was, however, not known if T3, or other hormones, could up-regulate ER mRNA in the absence of exogenous E2. We now show that T3 and dexamethasone (Dex), but not progesterone and testosterone, directly induce ER mRNA within 4 h by separate pathways, at doses compatible with the Kd values of their receptors. This induction of ER mRNA is accompanied by a marked enhancement of the activation of the silent Vit B1 gene if E2 is added by 12 h after T3 and Dex, thus suggesting an elevated level of functional ER induced by the two hormones. This conclusion was supported by a higher rate of transcription from an estrogen response element (ERE)-tk-CAT construct transfected into cultured hepatocytes pre-treated with T3 and Dex before incubation with estrogen. Our findings emphasize the importance of hormonal interplay via auto- and cross-regulation of nuclear hormone receptors.